期刊
JACC-CARDIOVASCULAR INTERVENTIONS
卷 11, 期 2, 页码 181-191出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jcin.2017.07.022
关键词
antiplatelet therapy; cardiovascular events; clopidogrel; CYP2C19; percutaneous coronary intervention; pharmacogenomics
资金
- National Institutes of Health (NIH) as part of the NIH IGNITE (Implementing Genomics in Practice) network [U01 HG007269, U01 HG007775, U01 HG007253, U01 HG007762]
- NIH (NIH Pharmacogenomics Research Network) [U01 GM074492, U01 HL105198, K23 HL112908, K23 GM112014, UL1TR0000005, R01HL092173, 1K24HL133373, UL1TR000165]
- Clinical Translational Science Institute [UL1 TR000064, UL1 TR001427]
- University of Maryland Medical Center
- University of Maryland School of Medicine Program for Personalized and Genomic Medicine
- American Society of Health System Pharmacists
- Penn Center for Precision Medicine at the Perelman School of Medicine at the University of Pennsylvania
- University of Alabama, Birmingham Health Service Foundations' General Endowment Fund
- Indiana University Health-Indiana University School of Medicine Strategic Research Initiative
- Haemonetics
- University of Illinois at Chicago Office of the Vice President for Health Affairs
- University of Illinois at Chicago Office of the Vice Chancellor for Research
OBJECTIVES This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value. (C) 2018 by the American College of Cardiology Foundation.
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